The present invention relates to antibacterial agents of the carbapenem class in which the five membered pyrroline ring of the carbapenem nucleus is substituted by various cationic --S-- heteroaryl substituents.
Thienamycin was an early carbapenem antibacterial agent having a broad spectrum; it has the following formula: ##STR2## Later, N-formimidoyl thienamycin was discovered; it has the formula: ##STR3##
The carbapenems of the present invention are useful against gram positive microorganisms, especially methicillin resistant Staphylococcus aureus (MRSA), methicillin resistant Staphylococcus epidermidis (MRSE), and methicillin resistant coagulase negative Staphylococci (MRCNS). Additionally, strains of vancomycin resistant enterococcus (VRE) have recently been reported. The antibacterial compounds of the present invention comprise an important contribution to therapy of these difficult to control pathogens. There is an increasing need for agents effective against such pathogens (MRSA/MRCNS and VRE) which are at the same time safe, i.e., relatively free from undesirable side effects.
Also, certain carbapenems of the present invention have a relatively low level of inactivation by dehydropeptidase and penicillinase, two enzymes known to reduce the serum levels of conventional beta lactam antibiotics.